title: Determination of artemether and dihydroartemisinin in human plasma with a new hydrogen peroxide stabilization method.
abstract: BACKGROUND
  Numerous methods have been reported for the determination of artemether (ARM) and its metabolite dihydroartemisinin (DHA) in plasma. However, stability issues in patient plasma have not received enough attention.
  
  
  RESULTS
  An LC-MS/MS method for simultaneous determination of ARM and DHA in human plasma (K3EDTA) turned out to be problematic: ARM and DHA were degraded partially or completely in some patient plasma samples as indicated by the stable isotope-labeled internal standards. We postulated iron II (Fe(2+)) in hemoglobin or its derived products from malaria patients causes degradation of the drugs, and found that hydrogen peroxide (H2O2) protected the drugs from degradation. Acidifying plasma increased recovery of ARM significantly. Using only 50 µl of plasma sample, the method has a LLOQ at 0.5 ng/ml for both ARM and DHA.
  
  
  CONCLUSIONS
  H2O2 is a stabilizing agent for artemisinin derivatives. The modified method is reliable and sensitive.
authors.affiliation: Drug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California-San Francisco, CA 94110, USA. huangl@sfghsom.ucsf.edu
authors.forename: Liusheng
authors.initials: L
authors.lastname: Huang
authors.forename: Alexander
authors.initials: A
authors.lastname: Olson
authors.forename: David
authors.initials: D
authors.lastname: Gingrich
authors.forename: Francesca T
authors.initials: FT
authors.lastname: Aweeka
mesh_terms: D000962:Antimalarials / Q000097:blood* / Q000378:metabolism; D000077549:Artemether; D037621:Artemisinins / Q000097:blood* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry*; D007553:Isotope Labeling; D053719:Tandem Mass Spectrometry; D013696:Temperature
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C039060:artenimol; D006861:Hydrogen Peroxide; D000077549:Artemether